Polymer refilling of presbyopic human lenses in vitro restores the ability to undergo accommodative changes

PURPOSE. Because presbyopia is thought to be accompanied by increased lens sclerosis this study was conducted to investigate whether refilling the capsule of the presbyopic human lens with a soft polymer would restore the ability of the lens to undergo accommodative changes. METHODS. Accommodative forces were applied to natural and refilled lenses by circumferential stretching through the ciliary body and zonular complex. Nine natural lenses and 10 refilled lenses from donors ranging in age from 17 to 60 years were studied. Two refill polymers with a different Young's modulus were used. The lens power was measured by a scanning laser ray-tracing technique, and lens diameter and lens thickness were measured simultaneously while the tension on the zonules was increased stepwise by outward pull on the ciliary body. RESULTS. In the natural lenses the older lenses were not able to undergo power changes with stretching of the ciliary body, whereas in the refilled lenses, all lenses showed power changes comparable to young, natural lenses. The refilled human lenses had a higher lens power than the age-matched natural lenses. The Young's modulus of the polymers influenced the lens power change when measured with the ciliary body diameter increased by 4 Him. CONCLUSIONS. Refilling presbyopic lenses with a soft polymer enabled restoration of lens power changes with mechanical stretching. Because sclerosis of the lens is an important factor in human presbyopia, refilling the lens during lens surgery for cataract could enable restoration of clear vision and accommodation in human presbyopia

Accommodative lens refilling in rhesus monkeys

PURPOSE. Accommodation can be restored to presbyopic human eyes by refilling the capsular bag with a soft polymer. This study was conducted to test whether accommodation, measurable as changes in optical refraction, can be restored with a newly developed refilling polymer in a rhesus monkey model. A specific intra-and postoperative treatment protocol was used to minimize postoperative inflammation and to delay capsular opacification. METHODS. Nine adolescent rhesus monkeys underwent refilling of the lens capsular bag with a polymer. In the first four monkeys (group A) the surgical procedure was followed by two weekly subconjunctival injections of corticosteroids. In a second group of five monkeys (group B) a treatment intended to delay the development of capsular opacification was applied during the surgery, and, in the postoperative period, eye drops and two subconjunctival injections of corticosteroids were applied. Accommodation was stimulated with carbachol iontophoresis or pilocarpine and was measured with a Hartinger refractometer at regular times during a follow-up period of 37 weeks in five monkeys. In one monkey, lens thickness changes were measured with A-scan ultrasound. RESULTS. In group A, refraction measurement was possible in one monkey. In the three other animals in group A, postoperative inflammation and capsular opacification prevented refraction measurements. In group B, the maximum accommodative amplitude of the surgically treated eyes was 6.3 D. In three monkeys the accommodative amplitude decreased to almost 0 D after 37 weeks. In the two other monkeys, the accommodative amplitude remained stable at +/- 4 D during the follow-up period. In group B, capsular opacification developed in the postoperative period, but refraction measurements could still be performed during the whole follow-up period of 37 weeks. CONCLUSIONS. A certain level of accommodation can be restored after lens refilling in adolescent rhesus monkeys. During the follow-up period refraction measurements were possible in all five monkeys that underwent the treatment designed to prevent inflammation and capsular opacification

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men &lt;= 50y, men &gt; 50y, women &lt;= 50y, women &gt; 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR&lt; 5%) age-specific effects, of which 11 had larger effects in younger (&lt; 50y) than in older adults (&gt;= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.</p

THE LIQUID-CRYSTALLINE MONOMER N-(PARA-METHACRYLOYLOXY-BENZYLIDENE)-PARA-AMINOBENZOIC ACID - ITS SYNTHESIS, CHARACTERIZATION AND POLYMERIZATION

The monomer N-(p-methacryloyloxy-benzylidene)-p-aminobenzoic acid (MOBAB) has been extensively investigated. Several crystallization methods were developed in order to obtain it in a pure state. MOBAB showed a complicated thermal behaviour depending on the purification procedure, drying and ageing. Crystallization from p-dioxane or mixtures with THF led to monoclinic needle-like crystals that contained one molecule of dioxane to two molecules of MOBAB, as confirmed from X-ray examination. From combined DSC, WAXS and microscopic results, the various thermal transitions in degrees-C (excluding those arising from solvents) could be assigned to [GRAPHICS] The interconversion between the K1 and K2 crystal forms may be caused by the existence of two conformers of the aromatic azomethine moiety, as supported by a conformational analysis and literature data. Radical polymerization of MOBAB in DMF showed classical features and led to low molar mass polymers with T(g) of about 130-degrees-C. The polymers showed some ordering, possibly arrising from frozen-in nematic structures. Solutions in DMF showed a polyelectrolyte effect

THERMAL-ISOMERIZATION OF AZOBENZENE-BASED ACRYLIC-MONOMERS AND (CO)POLYMERS WITH DIMETHYLAMINO SUBSTITUENTS IN SOLUTION - INFLUENCE OF ADDITION OF (POLY)ACID, COPOLYMER COMPOSITION, SPACER LENGTH, AND SOLVENT TYPE

This study reports on a method for influencing the thermal isomerization of azobenzene-based acrylic monomers and (co)polymers by means of interaction between basic polymeric and monomeric azobenzenes (modified with a basic dimethylamino substituent, (polyazobases) and (poly)acids. The results indicate that acid catalysis is the predominant effect, which is controlled by (inter)polymer cooperative hydrogen bonding, because on addition of the low molecular weight isobutyric acid (IBA) to the (polyazobases no effect was observed, and on addition of poly(methacrylic acid) (PMA) to the monomeric azobases only a weak effect was found. On addition of PMA, the rate constant of the thermal cis to trans isomerization (k(T-isom)) of a polyazobase could be enhanced by a factor of 70. The influences of factors like copolymer composition, spacer length, solvent type, and stabilization time after mixing on the thermal isomerization were also investigated and explained in terms of polymer complexation. In the absence of PMA the rate of the thermal isomerization was found to decrease by introduction of a spacer, by lowering the azobase monomer content in copolymers and by improving the solvent quality. The results on the thermal cis to trans isomerization presented here were obtained from measurements in dilute solution with concentrations well below c*, because in that case polymer matrix effects could be ruled out

PHOTORESPONSIVE BEHAVIOR OF AZOBENZENE-BASED (METH)ACRYLIC (CO)POLYMERS IN THIN-FILMS

The reversible photoisomerization and the thermal isomerization of azobenzene-based (Az.b.) groups covalently bound to (meth)acrylic (co)polymers were investigated in thin films. For the amorphous polymers it was found that a broad range of the thermal cis --> trans isomerization rates could be obtained by varying the substituent, spacer, and copolymer composition. The liquid crystalline (LC) polymers showed an interesting behavior of the orientation of the stable trans state when exposed to visible light, during which the orientation of the Az.b. groups changed from more or less random to more perpendicular (photoselection process). This change of orientation of the Az.b. groups may be suitable for optical data storage. In principle, the orientation change is permanent, but it can be easily erased by heating the LC polymer above its isotropization temperature, on which the original random orientation is largely restored